Saquinavir (SQV) is a human immunodeficiency virus (HIV) specific protease inhibitor. When combined with ritonavir (RTV), plasma concentration of SQV is increased. In this study, we examined pharmacokinetics of SQV soft-gel capsule (SQV-SGC) 400 mg twice daily (BID) combined with RTV in HIV-1-infected patients (n = 4) and compared with those of SQV hard-gel capsule (SQV-HGC) 400 mg BID combined with RTV (n = 12). Pharmacokinetics of SQV-SGC 1,200 mg single dose in healthy subjects (n = 10) were also studied. Peak SQV concentration in plasma (Cmax) and area under the plasma concentration-time curve from 0 to 8 hour (AUC0-8 h) of SQV-SGC 400 mg BID combined with RTV group were higher than those of SQV-HGC 400 mg BID combined with RTV group; increase of 14.7% and 25.5%, respectively. Cmax and AUC0-8 h of SQV-SGC were higher than SQV-SGC 1,200 mg single dose group; increase of 3.9 fold and 8.5 fold, respectively. These results indicated that SQV-SGC combined with RTV therapy is the most potent antiviral effect among SQV-SGC with RTV, SQV-HGC with RTV, and SQV-SGC alone.