The unicellular Tetrahymena is a sensitive model for the study of chemotaxis induced by endothelins. In short-term chemotactic responses, ET-2 and ET-3 were chemorepellent, compared to the referent control (culture medium) and chemoattractant, ET-1. These differences suggest that the change of some aromatic residues in the loop region (residues 5–9) of the ET-1 abrogates its chemoattractant character. The response of Tetrahymena is highly selective, since substitution of two amino acids are enough to cause this alteration in (behavioural) response. Such a change seems to be more important than the loss of the entire first 10 amino acids (in ET-1 fragment 11–21), since after this it acquires some chemoattractive effect of ET-1. Selection with ET-3 rigorously stimulated the cell's responsiveness to the medium, this ability was abolished by the repeated ET-3 treatment. Big endothelin-1 was repellent in all concentrations. These experiments demonstrate the very sensitive discriminating capacity of chemotactic responsiveness at a low level of phylogeny. Chemotactic selection with endothelins underlines the possibility that there may be separate mechanisms responsible for the short-term chemotactic responses and the long-lasting effects of chemotactic selection.