The present study was undertaken to evaluate the effect of phenobarbital (PB) on the development of neurogenic tumors induced in WF rats by neonatal administration of N-ethyl-N-nitrosourea (ENU; CAS: 759-73-9). Group I rats were given a single sc injection in the backs of 5 mg ENU/kg body weight within 24 hours after birth. In group II, continuous oral administration of 0.05% PB in the drinking water was commenced 4 weeks after birth. Following neonatal injection of ENU, administration of PB was commenced 4 weeks after birth in group III. Rats in group IV served as untreated controls. All groups consisted of about an equal number of both sexes of rats. The experiment was terminated when the rats were 52 weeks old. The incidence of all neurogenic tumors in both sexes combined was 11 of 26 (42%) in group I and 3 of 22 (14%) in group III (P greater than .05). The incidence of gliomas alone was 10 of 26 (38%) in group I and 2 of 22 (9%) in group III (P less than .05). When females and males were evaluated separately, the incidence of gliomas in females was 7 of 13 (54%) in group I and 1 of 12 (8.3%) in group III (P greater than .05), whereas in males, 3 of 13 (23%) in group I and 1 of 10 (10%) in group III (P greater than .05), the difference was not statistically significant. At the end of the experiment the mean serum level of PB in females (33.0 micrograms/ml) was significantly higher than that in males (19.8 micrograms/ml) (P less than .05). These data suggest an inhibitory effect of PB on the development of ENU-induced gliomas in female rats.