We examined the effects of SS320A ((-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid), a new cysteine derivative, on the change in the number of goblet cells induced by isoproterenol in rat tracheal epithelium. Four types of goblet cells were characterized in tracheal epithelium according to their size and staining affinity with Alcian blue (AB) / periodic acid Schiff (PAS). When each rat was given a single daily injection of isoproterenol (0.05 mg/kg, i.p.) for 14 days, a significant increase was observed in AB/PAS-positive cells that were recognizable as goblet cells in tracheal epithelium. When SS320A (10 - 100 mg/kg, p.o.) or propranolol (1 mg/kg, s.c.) was administered before each injection of isoproterenol, the increase in the number of goblet cells induced by isoproterenol was significantly inhibited. There was no difference between male and female rats with regard to this inhibitory action. On the other hand, ambroxol, bromhexine, L-cysteine ethyl ester and S-carboxymethylcysteine (100 mg/kg, p.o., respectively), which are used as expectorants, had no inhibitory effects on the isoproterenol-induced change in the number of goblet cells. Four metabolites (M1 - M4) of SS320A in rats also failed to inhibit the change induced by isoproterenol. These data suggest that SS320A itself may have a beneficial effect against mucus hypersecretion in chronic respiratory diseases.