In a 2-year bioassay, we exposed Fischer 344 rats to a frequency-modulated (FM) signal (836.55 MHz +/- 12.5 KHz deviation) simulating radiofrequency exposures in the head of users of hand-held mobile phones. We tested for effects on spontaneous tumorigenicity of central nervous system (CNS) tumors in the offspring of pregnant rats and also for modified incidence of primary CNS tumors in rats treated with a single dose of the neurocarcinogen ethylnitrosourea (ENU) in utero. ENU dosage (4 mg/kg) was selected to give an expected brain tumor incidence of 10-15% over the mean life span of 26 months. Pregnant dams (n = 102) were randomly assigned to six groups. Their offspring were treated as cohorts in each of the six groups (n = 90 per group; total, n = 540): Sham ENU/Sham Field, Sham ENU/Field Exposed, ENU/Sham Field, ENU/Field Exposed, ENU/Cage Control, and Sham ENU/Cage Control. Intermittent field exposures began on gestation day 19 and continued until weaning at 21 days, resuming thereafter at 31 days and continuing until experiment termination at 731-734 days. Energy absorption rates (SARs) in the rats' brains were similar to localized peak brain exposures of a phone user (female, 236 g, 1.0 W/kg; male, 450 g, 1.2 W/kg). Of the original 540 rats, 168 died before the termination of the experiment. In these rats, ENU significantly reduced survival from a mean of 708 days in three groups without ENU treatment to 645 days in three groups treated with ENU (P < 0.0005). There were no effects on survival attributable to FM field exposure in either ENU-treated or in sham-treated groups. Spontaneous CNS tumor incidence in control groups was 1.1-4.4% but sharply higher in rats receiving ENU (14.4-22.2%; P < 0.0001). No FM field-mediated changes were observed in number, incidence, or histological type of either spontaneous or ENU-induced brain tumors, nor were gender differences detected in tumor numbers. These negative findings with FM fields contrast with our study using standard digital phone fields pulsed on and off at 50/se, where a trend was noted toward reduced incidence of both spontaneous and ENU-induced CNS tumors (W. R. Adey et al., Radiat. Res., 152: 293-302, 1999). Although consistent but not attaining significance in the experiment overall (spontaneous CNS tumors, P < 0.08 one-tailed; P < 0.16 two-tailed; ENU-induced CNS tumors, P < 0.08 one-tailed, P < 0.16 two-tailed), the trend was significant (P < 0.015 one-tailed, P < 0.03, two-tailed) in rats that received ENU and died prior to experiment termination, with a primary brain tumor as the cause of death. We discuss differences in the signaling structure of digital and FM fields. Certain bioeffects induced by either amplitude-modulated or pulsed radiofrequency fields at athermal levels have not been seen with fields of similar average power but unvarying in intensity (continuous wave or frequency-modulated fields).