Previous experiments established that when the unicellular green alga Chlorella NC64A is inoculated with two viruses, usually only one virus replicates in a single cell. That is, the viruses mutually exclude one another. In the current study, we explore the possibility that virus-induced host membrane depolarization, at least partially caused by a virus-encoded K(+) channel (Kcv), is involved in this mutual exclusion. Two chlorella viruses, PBCV-1 and NY-2A, were chosen for the study because (i) they can be distinguished by real-time PCR and (ii) they exhibit differential sensitivity to Cs(+), a well-known K(+) channel blocker. PBCV-1-induced host membrane depolarization, Kcv channel activity and plaque formation are only slightly affected by Cs(+), whereas all three NY-2A-induced events are strongly inhibited by Cs(+). The addition of one virus 5-15 min before the other results primarily in replication of the first virus. However, if virus NY-2A-induced membrane depolarization of the host is blocked by Cs(+), PBCV-1 is not excluded. We conclude that virus-induced membrane depolarization is at least partially responsible for the exclusion phenomenon.