The aim of the present study was to test the effect of cyclosporin A (CyA) in vitro on CFU-GM growth from patients with severe aplastic anemia (SAA). For this purpose, bone marrow (BM) cells from 9 SAA patients and 5 healthy individuals were incubated with or without CyA and then cultured for CFU-GM growth in the presence of exogenous recombinant human GM-CSF (30 ng/ml). SAA patients were tested before or after treatment with CyA, or after treatment with antilymphocyte globulin (ALG). In 3 patients responding to CyA, the addition of CyA in vitro enhanced colony growth from 13 +/- 10 to 40 +/- 20/10(5) BM cells (p = 0.01) - the median increment of colony formation was 2.4-fold. In 5 ALG responders, CyA produced no increment of CFU-GM growth (from 14 +/- 26 to 15 +/- 16/10(5) BM cells, p = 0.1). CyA did not enhance significantly CFU-GM growth in normal controls (from 57 +/- 45 to 58 +/- 81/10(5) BM cells, p = 0.9). In conclusion, it would appear that some patients with SAA can respond to CyA in vivo and in vitro, and ALG responders are not necessarily among these. This is in keeping with different mechanisms of action of CyA and ALG and possibly with the existence of distinct pathogenetic pathways in SAA.