Reproductive and behavioral functions of progesterone receptors (PRs) in males were assessed by examining consequences of PR gene deletion. Basal hormone levels were measured in male progesterone receptor knockout (PRKO) mice and co red to wild-type (WT) counterparts. RIA of serum LH, testosterone and progesterone (P) levels revealed no significant differences. Levels of FSH were moderately but significantly lower and inhibin levels were higher in PRKOs; these differences were not accompanied by gross differences in testicular weight or morphology. PRKOs exhibited significant alterations in sexual behavior. In initial tests PRKOs exhibited reduced latency to mount compared with WT. In second sessions, PRKOs again showed a significantly reduced latency to mount, and increased likelihood of achieving ejaculation. RU486 treatment in WT produced increased mount and intromission frequency, and decreased latency to intromission. In anxiety-related behavior tests, PRKO mice exhibited intermediate anxiety levels compared with WT, suggesting that enhanced sexual behavior in PRKOs is not secondary to reduced anxiety. Immunohistochemical analysis revealed significantly enhanced androgen receptor (AR) expression in the medial preoptic nucleus (MPN) and bed nucleus of the stria terminalis (BST) of PRKO. We conclude that testicular development and function, and homeostatic regulation of the hypothalamic-pituitary-testicular axis are altered to a lesser extent by PR gene deletion. In contrast, PR appears to play a substantial role in inhibiting the anticipatory/motivational components of male sexual behavior in the mouse. The biological significance of this inhibitory mechanism and the extent to which it is mediated by reduced AR expression remain to be clarified.