Resting mouse splenic B cells were activated with lipopolysaccharide/dextran sulfate (LPS/DxS) to measure both B cell proliferation and IgM/IgG isotype production when increasing concentrations of [Met5]-enkephalin (MENK) and proenkephalin (PENK) (10-16 to 10(-8) M) were added at increasing times after B cell activation (0, 3, 6, or 24 h). Results show that proliferation was not affected by either peptide, but that IgM, IgG3 and IgG2a production were inhibited in a concentration- and time-dependent manner by MENK. IgG1 production was unaffected by MENK. In contrast, PENK induced no change in the production of Ig isotypes at any time point of addition, with the exception of IgG1 and IgG2a that were enhanced when PENK was added 6 h after cell activation. In the absence of LPS/DxS activation, no change in the level of any Ig isotype was induced by either peptide.