The existence of synergistic drug combinations against the in vitro replication of poliovirus type 1 (Mahoney) (PV-1) had been established in our previous work. The objective of the present study was to test the combined effects of the different drugs against another representative of the enterovirus genus, i.e. Coxsackievirus B1 (CBV-1). Dual combinations of enviroxime, disoxaril, arildone, PTU-23, HBB and S-7 were evaluated. The susceptibility of CBV-1 to the individual effects of the inhibitors was compared to that of PV-1. CBV-1 was more sensitive to enviroxime, S-7, PTU-23 and HBB and less sensitive to the effects of disoxaril and arildone. The effect of most dual drug combinations tested against CBV-1 replication was additive or synergistic. Enviroxime and S-7, enviroxime and PTU-23, disoxaril and HBB, disoxaril and PTU-23, arildone and HBB, arildone and PTU-23, S-7 and HBB revealed a strong synergistic effect. Synergy against CBV-1 replication was stronger as compared to that noted for the same drug combinations against PV-1 replication.