Ethnic differences in the outcome of hepatitis C have been described. Our aim was to investigate ethnic differences in the distribution of genotypes associated with polymorphisms of the tumor necrosis factor-alpha promoter, interleukin-10 promoter, and transforming growth factor-beta1 leader sequence in patients with hepatitis C. Genomic DNA was obtained from 71 Egyptians and 67 Caucasians (hepatitis C and control patients). Amplification of appropriate gene segments was followed by direct sequencing. Infrequently occurring polymorphisms were identified at positions -244 and -77 of the tumor necrosis factor-alpha promoter and at positions -851 and -657 of the interleukin-10 promoter. The G/A genotype associated with tumor necrosis factor-alpha promoter positions -376 and -244 was more frequent in Egyptians (P =0.001 and P =0.004, respectively). The -244 G/A genotype occurred only in healthy Egyptians (P =0.024). Thus, ethnic differences in the distribution of genotypes of the tumor necrosis factor-alpha promoter exist, which may have clinical implications on the outcome of hepatitis C.