Progesterone and its metabolites are potent depressors of the central nervous system. Plasma progesterone concentrations significantly correlated with temperament ratings for approach/withdrawal (r = -0.35, p = 0.01) and intensity (r = -0.28, p = 0.04) among 42 normal infants. The median age at the time of the progesterone sample was 36 days. Easier infants tended to have higher plasma progesterone concentrations compared with more difficult infants (mean +/- SEM: 25 +/- 4 ng/dl versus 17 +/- 3 ng/dl, p = 0.15). Results are consistent with the hypothesis that progesterone or its metabolites may exert a behavioral depressor effect in infancy.