INTERACTION of the lectins phytohaemagglutinin (PHA) and concanavalin A (con A) with the lymphocyte plasma membrane initiates a sequence of metabolic events leading to cell proliferation. The numerous alterations in cellular components and processes that occur early after mitogenic stimulation include enhanced uptake of nucleotides2, amino acids3,4, sugars5, Ca2+ (ref. 6), and K+ (ref. 7), enhanced activity of several membrane enzymes8,9, accelerated turnover of phospholipids10,11, increased membrane fluidity 12 and an increased accumulation of cellular cyclic 3′, 5′-guanosine monophosphate (cyclic GMP)13-15. Demonstrations that exogenous cyclic GMP can stimulate definable functions in lymphocytes 16,17, including proliferation18, and that there is an association between phytomitogen action and cyclic GMP accumulation suggest that this nucleotide is a positive effector of proliferation. To investigate further how cyclic GMP may be involved in this sequence of events, we have studied the effects that the oxidant periodate (IO4) and the reducing agent cysteine have on the cyclic nucleotide levels of rodent splenic cells 1. IO4 stimulates lymphocyte proliferation19 and because the oxidant produces definable chemical alterations in membrane components, which can be prevented by reducing agents20, studies with these agents may provide insights into the regulation of cyclic GMP metabolism in relation to mitogenic stimulation.