Many New World primates such as the squirrel monkey have extraordinarily high plasma steroid hormone levels as compared to humans and Old World primates. To clarify the mechanism(s) underlying this apparent steroid resistance, glucocorticoid and androgen binding to putative receptors in genital skin fibroblasts from several species was investigated. Differences in either affinity and/or number of binding sites were found but these were small compared to the very large differences in total or free plasma steroid concentrations between Old and New World primate species. In contrast, when the ability of fibroblasts to metabolize testosterone was compared, squirrel monkey cells were devoid of 5 alpha-reductase activity which was readily demonstrated in human cells. Together with other data indicating that squirrel monkeys excrete little if any 5 alpha- or 5 beta-reduced urinary steroid metabolites, these results suggest that inefficient metabolism rather than receptor binding abnormalities may account for the elevated plasma hormone levels in the squirrel monkey.