Nude and normal BALB/c mice were primed by intravenous inoculation of purified, infectious foot-and-mouth disease virus (FMDV) type A24, strain Cruzeiro. Frequency estimation of antigen-specific antibody-secreting cells (ASC) and Thy 1+ T cells in the spleens of immunized mice identified that the IgM response was similar for both nude and normal mice, whereas substantial numbers of both IgG ASC and Thy 1+ cells were present in normal mice only. In contrast, nude and normal mouse sera both contained IgG although the nude mouse serum was deficient in IgG1. Antigen-specific antibody could not be induced in spleen cell cultures from C57BL/6 mice after depletion of T cells with monoclonal antibody plus complement. However, the antibody response could be reconstituted if either a source of exogenous lymphokines or T cells from primed but not unprimed mice were added. Similarly, polyclonal stimulation or unprimed T cells could restore the in vitro response and thus complemented the finding of a low frequency of helper T cells in unprimed mice. Taken together, these data identify that the induction of IgG in FMDV-immunized mice is T cell-dependent and regulated by lymphokines. Furthermore, in nude mice a site other than the spleen must be responsible for the synthesis of the observed serum IgG.