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Glutathione S-transferases (GST) are a family of enzymes involved in phase-II detoxification of endogenous and xenobiotic compounds. Polymorphisms in GST genes have been associated with susceptibility to different diseases. In this study we determined the frequencies of polymorphisms in GSTM1, GSTT1, and GSTP1 in DNA of 138 children from Cameroon, presenting with uncomplicated malaria (N = 19), malaria with minor complications (N = 81), or severe malaria (N = 38). Analyses of GSTM1 and GSTT1 were performed using PCR-multiplex procedure, while GSTP1 was done by PCR-RFLP. Subjects presenting with malaria with complications were found more often of the GSTM1-null genotype (58–64%) as compared with those with uncomplicated malaria (32%), a difference that was statistically significant. We conclude that the GSTM1-null genotype is associated with malaria with complications.