A number of benzoic acid derivatives were investigated for their effect on anti-CD3-induced T-cell growth. In addition, the effect of this costimulation on cells both acutely and chronically infected with HIV was determined. 2, 5 substitution of the benzene ring was important for activity. The 2-chloro, 5-nitrobenzoic acid derivative was chosen for further study and crystallised as the readily soluble sodium salt (CNBA-Na). CNBA-Na augmented anti-CD3-stimulated PBMC proliferation in a dose dependent manner. Supernatants taken from cultures of acutely and chronically infected cells costimulated with anti-CD3/CNBA-Na showed no increase in HIV antigen release compared with cultures not treated with CNBA-Na. This data indicates that these compounds may have differential effects on uninfected and infected cells. The mechanism of action is not entirely clear but may involve the modification of biochemical signals generated from cell surface molecules such as CD28.