Basal and stimulated gastric hydrochloric acid secretion was studied in 22 chronic fistula ferrets during estrus and anestrus. Maximal doses of histamine, pentagastrin, and insulin, and basal secretion were assessed. Basal secretion was unaltered by estrus. During estrus acid output, concentration, and volume output after i. p. histamine were unaltered but peak concentration and volume were slightly increased after s.c. histamine, suggesting that a hepatic factor, related to route of administration, may have altered the histamine effect. Pentagastrin and insulin-induced stimulation was slightly increased during estrus in acid concentration, but output and volume were unchanged. Histamine and pentagastrin response kinetics generally followed the pattern, log Y = a + b (log X) + c (log X)2. Insulin responses were delayed, following the pattern, Y = a + bX + cX2. This study suggests that natural hormonal changes may slightly alter the gastric secretory responses to test agents in the ferret.