Abstract: BACKGROUND:It is now known regulatory effect of gaseous mediators in many bodily functions. These mediators include nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). However, detailed data on the regulatory role of each of these gasotransmitters (GTs) are still not sufficiently studied. OBJECTIVE:The aim of this study was to investigate on models of microrheological behaviour of intact red blood cells and their recovered ghosts of cellular responses to all three known gasotransmitters: NO, H2S, and CO. METHODS:In experiments with intact red blood cells (RBCs) and their recovered ghosts (filled with an isotonic solution of known viscosity), deformability (RBCD) and aggregation (RBCA) were recorded after incubation of cells with GT donors or stimulators of their endogenous synthesis. RESULTS:It was found that all three GT donors moderately increased the deformability of both intact RBCs and their recovered ghosts (by 5–10%, p < 0.05). In addition GT donors and substrates of their endogenous synthesis significantly reduced RBCA, from 20 to 37% (p < 0.01). Experiments with inhibition of soluble guanylate cyclase (s-GC) almost completely eliminated the RBCD increasing effect of GT donors CONCLUSION:In present study it was demonstrated that all three known gaseous mediators: NO, CO and H2S cause moderate statistically significant positive alterations in RBC deformability as well as a noticeable decrease in RBC aggregation. This was confirmed both in experiments with gasotransmitter donors and stimulators of GT endogenous synthesis. In addition, the data obtained suggest that RBC microrheological responses to the actions of all three GTs are associated with activation of the guanylate cyclase signalling cascade.