The ratio of individual 78 isotypes after primary and secondary immunization with SRBC was studied in the strain with a normal formation of IgG antibodies (A/J) and in the strain which responds predominantly by formation of IgM antibodies and only by a low IgG antibody response (C57BL/10ScSn, hereafter referred to as B10). The greatest differences were found in the amount of PFC which produce the IgG2a isotype. In B10 mice the IgG2a/IgM ratio is more than 100 times lower than in A/J mice. The so-called "natural antibodies" to SRBC were detected in both strains and were only of the IgM class; they were slightly higher in B10 mice. Using haemagglutination inhibition test we did not find greater differences between SRBC and erythrocytes of B10 mice than between SRBC and erythrocytes of A/J mice which might explain the lower levels of IgG antibodies after immunization with SRBC. T lymphocytes play an important role for the IgM-IgG switch. This activity of T lymphocytes can be partially substituted by certain substances like LPS or even CFA. We attempted therefore to influence the level of IgG in B10 mice by administration of 10 micrograms of LPS i.p. simultaneously with SRBC. In the high responder strain A/J the administration of LPS led predominantly to an increase in IgG-producing PFC, while the amount of IgM increased only slightly. The effect of LPS on B10 mice was somewhat different. It increased the level of IgG to such an extent that it was comparable to the level seen in A/J mice; however, it also increased the number of IgM-producing PFC so that the final ratio of IgG/IgM remained low in B10 mice.