We have studied the mechanisms governing the induction of class II major histocompatibility complex (MHC) antigens on murine B lymphocytes by B cell stimulatory factor-1 (BSF-1). BSF-1 induced a dramatic (10- to 15-fold) and selective increase in class II MHC antigen expression, as judged by flow cytometry. Analysis of radiolabeled membrane proteins on BSF-1-induced B cells also showed that the expression of class II MHC antigens was increased 10- to 15-fold. Biosynthetic labeling studies established that a selective increase in the translation of class II MHC molecules could be detected at 5 to 6 hr post-addition of BSF-1 to culture. After 16 hr of culture, when cell surface expression was induced 12- to 15-fold, biosynthesis rates of class II MHC antigens was induced fivefold to sixfold. The biosynthesis of the I region-associated invariant chain (Ii) was also enhanced. Actinomycin D abrogated the increased biosynthetic labeling of class II products, suggesting transcriptional regulation of expression. At 6 hr after addition of BSF-1, there was a twofold increase in the steady-stage level of class II mRNA, which was slightly increased at 16 hr. The BSF-1-induced increase in surface Ia antigen is dependent on new transcription and translation. However, posttranslational events that lead to a decrease in membrane antigen turnover rate or to an increase in protein stability probably also play a significant role in the hyperexpression of class II antigens on BSF-1-treated B lymphocytes.