Studies in the male rat have demonstrated that fasting is associated with a decrease in serum TSH concentrations. The present studies were performed to determine if gender influenced the serum TSH changes associated with fasting. In 8 of 10 experiments in male rats, serum TSH concentrations were significantly reduced in fasted compared to fed groups. In contrast, in none of the 9 experiments in female rats were serum TSH concentrations significantly reduced in the fasted groups. When all experiments were pooled, the decrease in the serum TSH concentration in the fasted rats compared to that in the fed rats was 55 +/- 4% (mean +/- SE) in males and 10 +/- 7% in females (P less than 0.001). In female rats ovariectomy did not result in a pattern in which fasting was associated with a decrease in serum TSH concentrations. Testosterone (T) was administered to male rats during fasting, but this treatment did not prevent the fasting-induced decrease in serum TSH concentrations. In gonadectomized male rats serum TSH concentrations were unchanged by fasting. However, if T was administered to gonadectomized male rats before and during fasting, serum TSH concentrations were significantly decreased in the fasted compared to the fed rats. These studies indicate that there is a sex difference in the serum TSH response to fasting in rats. The decline in serum TSH with fasting in the male rat is not mediated by a decline in serum T concentrations. Rather, T appears to maintain a process which increases the serum TSH concentration, and it is this process that is susceptible to inhibition by fasting.