Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational days 14, 15, 16, 17, 18 or 19 which resulted in various degrees of microencephaly. Offspring were tested on a two-way shuttle box avoidance and residential maze activity at 60-90 days of age. Rats treated on gestational day 19 (GD19) were severely impaired in the acquisition of the two-way shuttle box task whereas the other groups did not show any significant difference from controls. Spontaneous activity measured for 23 hr in the residential maze was altered as total, time-course and pattern depending on the time of MAM administration: treatment on GD14 prolonged exploratory behavior, treatment on GD15 and GD16 increased nocturnal activity, treatment on GD16 and GD17 induced changes in locomotion patterns and treatment on GD18 and GD19 decreased total activity. These findings indicate that treatment with MAM results in selective deficits in the acquisition of a shuttle box avoidance and alterations of locomotion patterns in the offspring which are dependent on the time of administration.