Extensive experimental evidence has shown that thymic hormones (or factors) affect and regulate the differentiation and function of T lymphocytes. However, little is known about the action, if any, of thymic hormones on B lymphocytes. This paper reports the results of an investigation of the effect of a calf thymic peptide preparation (TP) prepared in our laboratory, on the proliferation and differentiation of human B lymphocytes. TP at concentrations higher than 1 micrograms (protein)/ml inhibited the proliferative responses of human B lymphocytes to the stimulation by Staphylococcus aureus Cowen strain I (SAC) and F(ab')2 fragments of goat anti-human IgM, mu chain specific antibody (anti-mu). TP itself had neither toxic nor mitogenic effect on B cells. TP at concentrations of 60 and 100 micrograms/ml did not affect the differentiation of B cells driven by SAC and PWM in a reverse PFC assay, but appeared to suppress the production in some individuals of total IgG and IgM in culture supernatants in a PWM system. Preculture of B cells with 60 micrograms/ml of TP for 40 hrs showed a suppression of the proliferative response to SAC and anti-mu stimulation, suggesting that TP might act on cells directly and persistently for some time. When TP was added to the culture on day 0 or on day 1, a similar decrease of inhibition of B cell proliferation was observed. A decrease in monocytes from 15-17% to 5% did not appreciably influence the suppression of SAC- or anti-mu-induced proliferation of B cells by TP. These preliminary results suggest that a calf thymic peptides preparation might have some direct effect on B lymphocytes.