Pre-transplant blood transfusions (BT) improve the survival of kidney grafts. Apart from specific immunoregulation by T suppressor cells or anti-idiotypic antibodies, the role of non-specific immunoregulatory factors, such as prostaglandins is being discussed as a possible mechanism for this effect. We studied the in vitro prostanoid release from peripheral mononuclear cells following three deliberate blood transfusions. Twenty-five previously non-transfused dialysis patients were studied. Spontaneous and LPS-induced prostaglandin E (PGE) and thromboxane B2 (TXB2) were determined in cell-free culture supernatants by fluid phase RIA. Transfused patients exhibited a more rapid onset and steeper increase of prostanoid production. After 24 hours incubation, the spontaneous and LPS-induced PGE release of pre- and post-BT cells was significantly different (pre-BT: 2.1 and 5.1 ng/ml; post-3-BT: 5.0 and 7.9 ng/ml; p less than 0.01). Pre-BT cells released considerably lower amounts of TXB2 than post-BT cells (spontaneous release: 39 vs 88 ng/ml; LPS-induced release: 62 ng/ml vs 129 ng/ml; p less than 0.05). After correction for monocytes as defined by monoclonal antibodies, post-BT cells again showed increased prostanoid release as compared to pre-BT cells. Therefore, the enhanced PGE and TXB2 release of post-BT cells is not caused by an increase merely in the number of monocytes. Rather, BT appear to induce an enhanced release of prostanoids by activation of monocytes. We also found a correlation between the number of BT and the amount of prostanoid release.