Representatives of 3 types of side-chain analogs of distamycin A were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured [African green monkey kidney] cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, and DNA synthesis by purified HSV DNA polymerase. Distamycin A was the most active and toxic compound in all 3 antiviral tests. Several compounds showed no toxicity under the experimental conditions used but were still very active in the 3 antiviral tests.