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Three-hundred ninety-nine individuals living in seven populations of two Brazilian Indian tribes (Macushi and Igana River Indians) were tested for the phosphoglucomutase 1 (PGM 1), properdin factor B (BF), haptoglobin (HP), and α-1-antitrypsin (PI) systems. We observed significant internal heterogeneity in the two tribes for the PGM 1 alleles and in the Macushi for the HP markers. Frequencies in three of the four systems (the exception being BF) also show clear differences in the Macushi and Igana River Indians. Compared with other ethnic groups, South American Indians generally present high frequencies of PGM1*1B, BF*S, HP*1S, and PI*M3. On the other hand, PGM1*1A, PI*M1, and PI*M2 are reduced, and HP*1F is absent or rare. This is the first report about HP subtypes among American Indians.