Previously, we have shown that paraformaldehyde-fixed monocytes are able to fully complement, in terms of [3H]dThd incorporation, a primary stimulus delivered to purified T cells by monoclonal antibodies (mAb) reacting with CD3 or CD2 molecules. Here, we show that depending on the stimulus used (CD3 mAb or different pairs of CD2 mAb) HLA class I molecules from monocytes are directly involved in complementary signals provided to T cells. This was evidenced by the following observations: (a) mAb reacting with the heavy or light chain of class I molecules, or their Fab fragments, completely blocked proliferation of peripheral blood lymphocytes (PBL) activated by CD3 mAb; (b) mAb against the heavy chain of HLA class I but not against beta 2-microglobulin partially blocked (approximately equal to 50%) PBL activation by the CD2 "GT2 + T111" mAb pair but did not block activation by CD2 "D66 + T111" mAb; (c) this pattern of inhibition was observed when anti-class I mAb were used in the soluble phase or when they were bound to monocytes subsequently fixed with paraformaldehyde and cultivated with purified autologous T cells; (d) fixed monocytes are able to restore interleukin (IL) 2 receptor expression on purified T cells stimulated by CD3 mAb or CD2 "GT2 + T111", contrary to anti-HLA class I mAb-pretreated monocytes. The inhibitory effects of anti-HLA class I mAb bound to monocytes were not found to be reversed by recombinant IL2 or recombinant IL1. We assume that HLA class I would be involved in two or more signals delivered to T cells by monocytes, the requirement in those signals depending on the initial stimulus applied to T cells.(ABSTRACT TRUNCATED AT 250 WORDS)