Bacterial cell wall products such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP) have the capacity to enhance immune responses to antigens. The expression of surface class II major histocompatibility antigens and the costimulatory receptors CD18 and CD54/ICAM-1 (intercellular adhesion molecule) was used to evaluate the comparative influence of these immunostimulators. On monocytes, both LPS and MDP increased the expression of human leukocyte antigen (HLA)-DR (maximal at 6 hr), CD18 (maximal at 1-3 hr), and ICAM-1 (maximal at 18-24 hr for LPS and 12 hr for MDP) without increasing the production of superoxide. MDP-induced ICAM-1 expression on monocytes returned to baseline values after 12 hr. On lymphocytes, only LPS increased ICAM-1 (after 18 hr) without affecting CD18, and a differential analysis demonstrated a generalized ICAM-1 upregulation in lymphocyte subsets after 18 hr: the most pronounced effect was measured in natural killer cells, followed by CD8(+) T cells, B cells, and CD4(+) T cells. MDP did not alter ICAM-1 or CD18 expression on lymphocytes. These similar but smaller effects of MDP may, in part, explain the lesser toxicity of MDP when compared to LPS.