The effect of aphidicolin on DNA synthesis in herpes simplex virus type 1 (HSV-1) infected and uninfected Vero cells was determined by isodensity banding of [32P]-labelled DNA. A 50% inhibition of HSV-1 DNA synthesis was observed at 0.07 microM aphidicolin while 2.1 and 1.3 microM were required to inhibit the cellular DNA synthesis to 50% in infected and uninfected Vero cells, respectively. When the viral DNA synthesis was totally inhibited by 10 microM aphidicolin, the cellular DNA synthesis was inhibited to about 90% in both infected and uninfected cells. Aphidicolin inhibited the cellular DNA synthesis in HSV-1 infected and uninfected Vero cells remaining in the presence of 250 microM foscarnet to the same extent as the DNA synthesis in the absence of foscarnet.