Macrophages can be stimulated to produce a relatively large amount of nitric oxide, which is an important component in macrophage-mediated defense mechanisms and regulation of T cell activities. It has been known that T helper (Th) cell activation requires intimate physical interaction between T helper cells and macrophages and that cytokines from activated Th cells regulate macrophage activities including nitric oxide production. The current study indicates that surface molecules on activated Th cells also can synergize with cytokines to substantially enhance nitric oxide production by macrophages through cell-cell contact. The CD40 ligand (gp39) and LFA-1 appear to be two major contributors for T cell dependent nitric oxide production.