The immunoglobulin (Ig)E, IgG subclass, and IgM formation in vivo and in vitro were measured by radioimmunoassays in normal and immunodeficient mice infected with the parasite Nippostrongylus brasiliensis (Nbr). High IgE responder mice had higher IgE serum levels than low responder mice both before (100 to 250 vs 2 to 20 ng of IgE/ml) and after (17,000 to 27,000 vs 1,000 to 5,000 ng of IgE/ml) infection. In vitro, mesenteric lymph node cells formed 5- to 10-fold more IgE than the spleen cells. Nu/nu mice had less than 1 ng before and 5 ng of IgE/ml serum after Nbr infection; no IgE was detectable in cell supernatants. There was no difference in the in vivo and in vitro IgE formation between C57BL/6 and C57BL/6-beige mice. Both in vivo and in vitro Nbr-infected Xid+ mice (CBA/N; (CBA/N X BALB/c) F1 male) formed approximately twice the amount of IgE than Xid- mice. Concomitant with the rise of the IgE serum levels, the IgG1 serum level increased by 100 to 1,500 micrograms/ml over preinfection levels in all strains except nu/nu+ mice. The IgM serum level increased by 100 to 500 micrograms/ml. In contrast, the IgG2a and IgG2b levels decreased in most strains, and the IgG3 levels remained unchanged. Nu/nu+ mice showed an increase of all IgG subclasses after Nbr infection. The antibodies to an Nbr extract were predominantly of IgM and IgG1, except in SJL mice which also had IgG2b and nude mice which only had IgM antibodies. The concomitant increase of IgE and IgG1 formation in all but the nude strains suggests that the regulation of these two Ig isotypes may be linked via regulatory T helper cells, which corroborates recent data on the simultaneous induction of IgG1 and IgE synthesis in vitro by the B cell stimulatory factor 1.