Strains of Leishmania braziliensis subspecies isolated from initial and recurrent lesions in 24 patients from the Pacific coast of Colombia were examined for distinguishing polymorphisms by enzyme electrophoresis, restriction endonuclease analysis of kDNA, and molecular karyotyping of nuclear DNA. Recurrent strains from 12 patients (50%) were identical to the initially infecting strain by all methods of characterisation. Phenotypic and genotypic identity, together with clinical data, support endogenous reactivation as the mechanisms of recurrent disease in these 12 patients. 5 of the 24 (22%) recurrent strains differed from the initial strain by all methods. The remaining 7 strain pairs, not separated by enzyme polymorphisms, showed differing schizodeme and/or karyotype profiles. Patients whose recurrent lesions were caused by strains different from those causing the initial lesions had a significantly longer disease-free interval than patients whose lesions were caused by identical strains. Recurrent lesions occurred further from initial lesions in the former than in the latter group. Exogenous reinfection is the most plausible explanation for recurrences due to disparate organisms. These findings have important implications for both treatment evaluation and vaccination strategies for American tegumentary leishmaniasis.