The capability of herpes simplex virus type 1 (HSV-1), strain Angelotti (ANG), to replicate in human promyelocytic HL-60 cells treated with 1,2-tetradecanoyl-phorbol-13-acetate (TPA) and dimethyl sulfoxide (DMSO) was examined. Virus titrations and infectious center assays revealed that HSV-1 ANG replicated in nontreated HL-60 cells and in HL-60 cells treated with TPA. An abortive infection was observed in DMSO-stimulated HL-60 cells. Viral DNA synthesis was detected in nontreated and TPA-treated cells, but not in DMSO-treated cells. Analysis of HSV-1 transcripts revealed that albeit the differences in pretreatment, HL-60 cells synthesized viral immediate-early (ICP4) and early (tk and pol) RNAs, whereas a late viral transcript (gC) was almost exclusively detected in nontreated and TPA-treated HL-60 cells. In line with these observations were the results obtained from studies on viral protein synthesis. The immediate-early protein ICP4 was found in all three cell types. Early (pol), delayed-early (gB), as well as late proteins (VP 5, gC) were identified in nontreated and TPA-treated cells, but only in reduced amounts in DMSO-treated cells. These data suggest a translational block of HSV replication in DMSO-treated HL-60 cells at the level of early gene expression.