In an attempt to elucidate the nature of the binding of PHA to lymphocytes, these cells were exposed to different enzymes before cultivation with PHA. The degree of stimulation was measured as 14C-thymidine incorporation into the acid insoluble fraction. It appears that certain enzymes, known to act on cell surfaces, suppress the PHA response while others leave it unchanged or even enhance the PHA effect. Trypsin and neuraminidase belong to the former group. Several hours after enzyme digestion lymphocytes are refractory to PHA treatment but gradually they recover their potential, implying that a regeneration of the surface has to occur before the PHA response can be initiated. Common monosaccharides had little or no effect on the PHA stimulation. © 1969.