The interactions among hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) were studied by measuring HBV-DNA and HCV-RNA levels and by determining the influence of viral genotypes and mutations in HBV basal core promoter (BCP) and precore regions. We included 65 consecutive patients, 25 HBV/HCV, 18 HBV/HDV, and 22 HBV/HCV/HDV. Controls consisted of 55 patients with chronic HBV and 55 with chronic HCV infection. HBV-DNA and HCV-RNA levels were lower in coinfections than in single infections (P < .05). HBV/HCV coinfection was associated with lower HBV viremia (8.2 × 104 copies/mL) and lower HCV-RNA levels (7 × 105 IU/mL), than the corresponding control group (P < .05), with more marked decrease in HBV replication (P < .05). Moreover, in HBV/HCV coinfection and in triple coinfection we observed an inverse relationship between HBV-DNA and HCV-RNA levels (P < .05). HBV/HDV coinfection was associated with lower HBV viremia (2.5 × 104 copies/mL) than that found in HBV infection (P < .05). Patients with triple coinfection showed lower HBV-DNA and HCV-RNA levels than control groups (P < .05). Prevalence of precore mutations was lower in HCV coinfections (P < .05). No significant association was observed between HCV-RNA levels and HBV precore mutations, BCP mutations or HBV genotypes, or between HBV-DNA levels and HCV genotypes (P < .05). In conclusion, HCV exhibited stronger inhibitory action in the reciprocal inhibition seen in HBV/HCV coinfection. HDV was the dominant virus in HBV/HDV coinfection and in triple coinfection, and had a greater unfavorable influence on HCV than on HBV replication. The reciprocal inhibition of viral replication seemed to be little influenced by the inherent genomic factors studied.