The magnitude of the IgE antibody response against the phosphorylcholine (PC) hapten and the rate of age-related change of IgE formation is polymorphic in the three long-lived and six relatively short-lived strains of mice studied. Long-lived mice showed an early increase, followed by a decline in the levels of anti-PC IgE antibody. The rate of increase and decrease was strain dependent. Among short-lived strains, MRL/Mp-lpr and MRL/Mp-+ mice showed an early decline in IgE antibody. The extent and rate of decline with age was more rapid in MRL/Mp-lpr animals than in MRL/Mp-+ mice. In contrast, there was an early increase of IgE antibody in female SJL, NZB/BIN, BXSB/Mp and male BXSB/Mp. Thus, opposite age-related changes in IgE antibody production can occur in animals with a tendency to develop autoimmune disease. In hybrids of (SJL X BALB/c)F1 and (BALB/c X MRL/Mp-lpr)F1, the levels of IgE antibodies were higher than those observed in either parental strain, and declined steeply with advancing age. We suggest that this could be attributed to recessive inheritance.