Serum levels of N-acetyl-beta-hexosaminidase (HEX) (EC 3.2.1.30) activity in infants display a sexual dimorphism. Total HEX activity in males between 1 and 3 months of age is significantly elevated over female levels (male (M), 1535 +/- 300 nmol/60 min/ml; female (F), 1150 +/- 203, P < 0.0005), and the A (labile) isozyme constitutes a significantly lower proportion of the total activity present (M, 56.0 +/- 4.2, N = 24; F, 64.3 +/- 4.6, N = 21, P < 0.0005). These findings led us to investigate the relationship between testosterone concentration and HEX activity in serum. Samples from male (N = 36) and female (N = 33) infants between 1 and 6 months of age were included. In both sexes, a high degree of correlation (P < 0.0005) was observed between testosterone and total HEX (M, r = 0.71; F, r = 0.73), HEX A (M, r = 0.68; F, r = 0.56) and HEX B (M, r = 0.68; F, r = 0.72). An inverse relationship exists between testosterone levels and % A: M, r = -0.56; F, r = -0.38 (P < 0.0025 and 0.025, respectively). In contrast, no correlation between HEX levels and testosterone was evident in either male or female adults (r = 0.20 and 0.18, respectively). These data implicate testosterone in the regulation of HEX activity during the early months of human development.