A novel series of 2-indolinones with in vitro anti-HIV (human immunodeficiency virus) activity is described. Two structurally related compound, 1, 3,3-(4-N-methyl-1,2,5,6-tetrahydropyridylmethyl)-1-phenyl-2- indolinone, and 2, its 4-N-methylpiperidinylmethyl analogue, formed the basis of a structure-activity study. The synthesis of approximately 50 analogues and their respective activities vs. HIV are presented. Both 1 and 2 were effective inhibitors of HV(IIIb) in cell protection assays with IC90 values of 4.4 and 14.9 μM (2.2 and 7.9 μg ml-1), respectively. In the same concentration range, 1 and 2 also inhibit syncytia formation. These compounds represent a novel class of anti-HIV agents which appear to act by inhibiting virus-dependent cell fusion.