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Abstract: Objectives: To investigate the genetic variability of multiple drug resistant 1 (MDR1) gene C3435T polymorphism in four Southern Chinese populations. Methods: Using discrimination real-time PCR, we determined the MDR1 C3435T polymorphism in three ethnic minority groups Lahu (n =104), Wa (n =101) and Bulang (n =100) in Yunnan Province, and Han Chinese (n =199) in Hong Kong. All of them were residents in Southern China. Results: For 3435 CC genotype, the frequency in Han Chinese in Hong Kong (44.7%) is significantly higher than in Lahu (16.3%) and Wa (29.7%) minorities, P <0.05. For 3435 CT genotype, the frequency in Han Chinese in Hong Kong (44.2%) is lower than in Lahu (58.7%), P <0.05. For 3435 TT genotype, frequency in Han Chinese in Hong Kong (11.1%) is lower than in Lahu (25%) and Wa (20.8%), P <0.05. For 3435 C allele, frequency in Han Chinese in Hong Kong (66.8%) is higher than in Lahu (45.7%) and Wa (54.5%), P <0.01. For 3435T allele, frequency in Han Chinese in Hong Kong (33.2%) is lower than in Lahu (54.3%) and Wa (45.5%), P <0.01. For MDR1 3435T allele, the frequencies are significantly higher in our four Southern Chinese populations than in African population (P <0.001) and significantly lower than in South-west Asians (P <0.05); Han Chinese in Hong Kong displayed significant difference from all the other ethnic populations except Japanese (P <0.05); compared with Caucasian and other ethnic Asians, Lahu minority showed no frequency difference (P >0.05) between Caucasian and other Asians (except Japanese). Conclusions: This is the first study to show the C3435T polymorphism of MDR1 in Southern Chinese populations. The frequency of C3435T, an important determinant for multidrug resistance, displays significant difference in ethnics. It may help for individualizing therapy for cancer, HIV and other common diseases. [Copyright &y& Elsevier]