Several organophosphorus compounds (OP) used commercially as flame retardants and plasticizers and related chemicals were evaluated for their effects on human in vitro cell-mediated immune responses. At nontoxic concentrations ranging from 0.1 to 20 microM, two of the tested compounds, triphenylphosphine oxide (TPPO) and tetra-o-cresylpiperazinyl diphosphoamidate (TCPD) caused significant suppression of antigen-specific lymphocyte proliferation (P less than 0.01). Mitogenesis was less sensitive to OP treatment and was affected only by TCPD. When monocytes and lymphocytes were treated separately with OP, washed, and recombined, it appeared that these OP mediated their suppressive effects by interfering with a monocyte function rather than acting directly on lymphocytes. Further, triphenyl phosphate (TPP), triphenyl thiophosphate (TPTP) as well as TPPO and TCPD were tested for direct inhibition of monocyte antigen presentation, and all four compounds were found to cause significant inhibition at concentrations as low as 1 microM (P less than 0.001).