Hepatitis C virus (HCV) genotypes help to tailor the treatment response, but their influence on the disease severity and association with hepatic steatosis is not well understood. The prevalence of HCV genotypes and their correlation with the histopathological severity of liver disease and steatosis in Indian patients were studied. HCV-RNA and genotyping was carried out in 398 patients with chronic hepatitis C. Liver biopsy was available in 292 (73.4%) patients. The severity of liver disease was graded on the basis of the histological activity index and the stage of hepatic fibrosis. The patients were categorized as having mild (histological activity index < or =5 and/or fibrosis < or =2) or severe (histological activity index > or =6 and/or fibrosis > or =3) liver disease. Steatosis was graded in 106 patients as 0 (no steatosis), 1 (<33% of hepatocytes affected), 2 (33%-66% of hepatocytes affected), or 3 (>66% of hepatocytes affected). HCV genotype 3 was detected in 80.2% patients (3a:24.4%, 3b:3.3%, 3c:0.5%, 3a/3b:36.7%, and un-subtypable 3:15.3%), genotype 1 in 13.1% (1a:3%, 1b:5.5%, 1a/1b:0.3%, and un-subtypable 1:4.3%), genotype 4 in 3% patients (4a:1.5%, 4b:0.3%, 4a/4c:0.5%, and un-subtypable 4:0.8%), 2 in 2.5% and mixed genotypes (more than one genotype) in 1.3% of patients. The median histological activity index and fibrosis scores were: 5 and 2 in genotype 1; 4 and 2 in genotype 2; 5 and 2 in genotype 3; 7 and 3 in genotype 4; and 5 and 2 in mixed genotypes, respectively. Severe liver disease was present in 17 of 38 (45%) with genotype 1; in 1 of 3 (33%) with genotype 2; in 128 of 236 (54%) with genotype 3; 7 of 10 (70%) with genotype 4; and in 1 of 4 (25%) with mixed genotype. Hepatic steatosis grade > or =2 was found in 28.1% of genotype 3; 23.5% of genotype 1; 20% of genotype 4; and in none of genotype 2 and mixed genotypes. In conclusion, genotype 3 is the most prevalent genotype in patients with chronic hepatitis C in North and Central India and this is associated with significant hepatic steatosis and fibrosis.