OBJECTIVE Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) demonstrate an affinity towards lymphocytes B, stimulating the production of cryoglobulins. Deposits of cryoprecipitates contribute to glomerulonephritis and renal failure. The presence of cryoglobulins was investigated in the sera of HCV-monoinfected and HCV/HIV-coinfected individuals. Associations between types of cryoglobulins and HCV genotypes, viral load and renal function tests were also evaluated. METHODS Seventy-seven patients were enrolled in this study. Forty-four were HCV infected and 33 were HCV/HIV coinfected. Cryoglobulins were detected in the sera by electrophoresis and immunofixation. Serum urea and creatinine concentration, glomerular filtration rate (GFR) and serum cystatin C concentration (CC) were analysed to evaluate renal function. The control group included 16 healthy individuals. RESULTS The occurrence of cryoglobulinaemia in HCV-monoinfected patients was 55%, whereas in HCV/HIV-coinfected patients it was 64%. Mixed cryoglobulinaemia type II was determined in 34%, whereas type III in 25%. The prevalence of cryoglobulinaemia was significantly higher in infection with HCV genotype 1 vs. genotype 3 (65 vs. 50%; P<0.01). The most frequently occurring heavy chains were gamma-type (96%). Light chains, the kappa-type, were detected in all patients. The CC concentration was significantly higher in HCV/HIV-coinfected patients compared with controls (718 vs. 392 ng/ml; P<0.005) or HCV-monoinfected patients (508 ng/ml; P<0.007). There was correlation between the serum CC concentration and the incidence of cryoglobulinaemia (R=0.44; P<0.00015), which was particularly evident in HCV monoinfection (R=0.43; P<0.0034). CONCLUSIONS Genotype-1 infection is an important risk factor for cryoglobulinaemia. Standard renal function tests are not sufficient for the prediction of renal failure in HCV-infected patients. Serum CC concentration allows to establish an early diagnosis of renal insufficiency related to cryoglobulinaemia.