The MAC for halothane is 25% lower in pregnant than that in nonpregnant ewes. The reason for this is uncertain, but changes in both steroidal and endogenous opiate have been implicated. This study was undertaken to assess the effect of exogenous progesterone on minimal alveolar concentrations (MAC) of halothane in ovariectomized rabbits. Minimal alveolar concentration of halothane was determined in 84 female rabbits, 37 intact (group A), 20 ovariectomized and injected with inert carrier peanut oil (group B), and 27 ovariectomized and injected with progesterone in peanut oil (group C). Minimal alveolar concentration in group A, 1.68 +/- 0.06% (mean +/- SEM), did not differ significantly from that in group B rabbits, 1.77 +/- 0.06%. However, MAC in progesterone-treated rabbits, 1.48 +/- 0.06%, was significantly lower than the MAC of the other two groups (P less than 0.01). Plasma progesterone concentrations in group A, B, and C were 5.28 +/- 0.62 ng/ml, 6.83 +/- 2.00 ng/ml, and 37.33 +/- 4.25 ng/ml, respectively. These results suggest that experimental treatment with progesterone can reduce the amount of halothane required to produce anesthesia and may explain the phenomenon of decreased need of inhalation anesthetic in human parturients.