This study aimed to investigate the performance of ELISA based tests for the detection of HIV in an adolescent population (n=7333) in the Mwanza Region of Tanzania. False positive results were observed with all the HIV ELISA tests examined during the study. When tested on serum the Murex Abbott HIV Ag/Ab Combination ELISA, a fourth generation ELISA test, gave HIV false positive results for 8% the population. This test had a positive predicative value of 7.72 in this population which had a HIV prevalence of 0.72%. Positive predictive values of 6 further tests examined ranged from 30.00 - 91.11 %. A critical review of the published literature determined that HIV ELISA specificities were lower in Africa when compared to the developed world. Investigation of treatments that were received by individuals within the study cohort, suggested an association of false positive HIV test results and schistosomiasis infection. Laboratory studies to investigate possible causal factors of false positive ELISA test results determined that false positivity was associated with increasing circulating levels of S. haematobium worm IgG 1 (OR = 53.5, Cl = 10.6-268.9); with increasing S. mansoni egg 19G1 levels (OR = 2.5, Cl = 0.7-8.7); and rheumatoid factor titre (OR = 5.6, Cl = 2.0-15.9). Circulating antibodies to malaria and syphilis were not associated with false positive HIV test results. The poor specificity of the HIV ELISA tests observed in this study suggests they may be unsuitable for testing African adolescent populations, particularly in those regions where schistosomiasis is endemic. We recommend that prior to introducing new HIV tests to sub- Saharan Africa they should be evaluated using local specimens to enable assessment of their specificity.