A total of 6002 blood samples from total population samples in four separate areas within Karonga District, Northern Malawi, were tested for anti-Mycobacterium leprae antibody using an ELISA based on synthetic glycoconjugate antigen. Results are presented using different criteria for seropositivity. Regardless of the criterion used, the proportion of individuals classified as "positive" rose to a peak at 20-30 years of age and then fell, and it was higher at all ages in females than in males. There was no difference in seropositivity levels between individuals with or without BCG scars. Although leprosy cases, in particular those with positive smears, had higher antibody levels than nonleprosy cases, analysis of age-standardized data revealed only weak evidence for a correlation between the prevalence rates of clinical leprosy and of seropositivity within the four areas. There was no evidence for higher seropositivity levels in household contacts of leprosy cases compared to noncontacts. The implications of these results for the epidemiology of leprosy in this population are discussed.