Neonatal B cells with the naive (sIgD+) phenotype are able to generate IgG- and IgA-producing cells as well as IgM production in the presence of memory CD4+ T cells expressing L-selectin (CD62L) in pokeweed mitogen-stimulated cultures. We used this system to examine comparatively the ability of naive B cells to produce IgG and IgA subclasses in newborn infants and adult individuals. Naive B cells were enriched from both donors on the basis of sIgD positivity, and memory (CD45RO+) CD4+ T cells with CD62L expression were isolated from adults. We here demonstrate some differences in profiles of IgG and IgA subclass production between neonatal and adult naive B cells. In neonatal B cells, IgG1 and IgG3 were predominantly produced, but IgG2 and IgG4 production was virtually absent. Similar to neonatal B cells, adult naive B cells produced mainly IgG1 and IgG3, although memory (sIgD-) B cells from adults secreted all of the IgG subclasses. It should be noted that low but detectable levels of IgG2 and IgG4 were found in adults' naive B cell cultures. Although IgA produced by neonatal B cells was exclusively IgA1, IgA2-secreting cells were identifiable in adult naive B cells. The results suggest that further class switch of naive B cells to IgG2, IgG4 and IgA2 in addition to IgG1 and IgG3 may be controlled by their own age-dependent maturation process.