The effect of phenyl- and benzylphthalimide analogs on tumor necrosis factor (TNF)-alpha production by a human leukemia cell line, HL-60, stimulated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was investigated. Though non-substituted phenyl- and benzyl-phthalimide had no effect on TNF-alpha production after TPA-induction, introduction of methyl group(s) onto the phenyl group resulted in the appearance of potent enhancing activity on TNF-alpha production.