The monitoring of blood, urine, throat, and tissue specimens for the presence of cytomegalovirus (CMV) is important for determining changes in the clinical status of patients infected with human immunodeficiency virus (HIV 1). We are currently studying patients on experimental therapies for HIV 1 infection and AIDS related opportunistic infections (such as CMV) to determine if treatment of the primary infections results in changes in CMV status. Foscarnet (trisodium phosphonoformate) is an antiviral agent with in vitro activity against both herpesviruses (including CMV), and HIV 1. We are currently participating in a randomized trial of AIDS patients with CMV retinitis, to determine the toxicity and efficacy of foscarnet plus AZT combination treatment. It appears that immediate treatment with foscarnet is more effective than delayed therapy in postponing progression of CMV retinitis. CMV vinemia cleared in 1 week and viruria in 2 weeks on induction therapy. A decrease in p24 antigen levels was also documented. With both anti-CMV and anti-HIV activity, foscarnet may become an important treatment of CMV retinitis in patients with AIDS. In addition, a trial was initiated to compare foscarnet and ganciclovir treatments in AIDS patients with CMV retinitis. In a separate in vitro study, we tested two drugs, foscarnet and gancyclovir separately and in combination for their anti CMV virostatic effects. It was found that the combination of the two drugs has a synergistic inhibitory effect on CMV replication. These in vitro findings may result in patient treatment with this drug combination allowing for use of reduced doses of the individual drugs and thus reducing the drug associated toxicity while obtaining a comparable level of antiviral activity.