We have examined the immune response against the nonimmunogenic heat-stable enterotoxin (STa) of enterotoxigenic Escherichia coli using recombinant fusion proteins containing the STa-peptide linked to an IgG-binding analogue of protein A and varying numbers of the T helper epitope 323-339 from ovalbumin (ova). By immunization of inbred strains of mice with a series of STa fusion proteins, containing up to four copies of ova tandemly multiplied, we demonstrated that the anti-STa antibody response is controlled by ova-specific T helper cells in a genetically restricted manner. In the responding mouse strains (2 out of 3 tested), the level of antibody production was increased by addition of multiple ova epitopes, the anti-STa response being considerably higher to fusion proteins containing four than one or two ova epitopes.