In the human menstrual cycle, luteal phase immunomodulation prevents the maternal immune system from attacking the half-foreign blastocyst should conception occur, thereby facilitating implantation and development. However, tolerance of the conceptus comes at the cost of increased vulnerability to infection. The compensatory behavioral prophylaxis hypothesis (Fessler, 2001; Fessler & Navarrete, 2003) holds that evolved psychological mechanisms enhance avoidance of potential contaminants during periods of reproductive immunomodulation so as to decrease the likelihood of infection. Because such immunomodulation is triggered by progesterone, this hormone is predicted to correspondingly enhance behavioral prophylaxis and the motivational states underlying it. We investigated specific domains of disease avoidance psychology in a nonclinical sample of women (n = 120) by measuring salivary progesterone in naturally cycling women. We find that progesterone correlates directly with the degree to which women report emotions, thoughts, and behaviors consonant with enhanced prophylaxis.