Activity of soluble guanylate cyclase and regulation of the enzyme were studied in thrombocytes of intact rats and under conditions of acute myocardial ischemia caused by ligation of left coronary artery. Distinct decrease in the enzymatic activity was detected already within 15 min after the operation: down to 19% and 46%, in presence of Mg2+ and Mn2+, respectively, as compared with control values. Within 24 hrs of the ischemia the guanylate cyclase activity was slightly increased up to 33.5% in Mg2(+)-containing mixture and was unaltered (46%) in presence of Mn2+. Considerable activation of the enzyme by 2.10(-4) M dithiotreitol (from 288% to 790%, respectively) was observed after 15 min of myocardial ischemia with subsequent normalization (down to 340%) within 24 hrs. The data obtained suggest elevation of free-radical reactions, specific for myocardial ischemia, as well as high sensitivity of guanylate cyclase in thrombocytes to these reactions beginning from the early steps of the disease. Absence of the sodium nitroprusside stimulating effect on rat thrombocyte guanylate cyclase, found under conditions of both normal state and myocardial ischemia, may be due to initial hemdeficiency of the enzyme.