SummaryPrevious work by Hafkemeyer et a/. (1991) [Nucleic Acids Research 19: [4059][4060][4061][4062][4063][4064][4065] indicated that a degradation product of ceftazidime, termed HP 0.35, was active against the RNase H activity of human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) reverse transcriptase (RT) in vitro. Attempting to repeat these results, we isolated HP 0.35 from an aqueous degradation of ceftazidime and, after careful purification, we found HP 0.35 to be essentially inactive against both the polymerase and RNase H domains of HIV-1 RT (IC 50 of>100 I1g mL-1). During the investigation we discovered that polymeric degradation products of ceftazidime inhibited both the polymerase and, to a greater extent, the RNase H activities of HIV-1 RT in vitro (IC 50 approximately 0.1 and 0.01 I1g mt', respectively). Subjecting HP 0.35 to conditions under which it could polymerize induced inhibitory activity similar to that of the polymeric ceftazidime degradation products. It is proposed that the previously reported activity of HP 0.35 may have resulted from the presence of low levels of polymeric material either from incomplete purification or from polymerization of HP 0.35 during storage or in vitro testing.