Ma et al. (2002) demonstrated that the thiazolidinone CFTR_inh172 is a potent, specific inhibitor of the cystic fibrosis transmembrane conductance regulator (CFTR). Knowing that CFTR plays an important role in renal cyst growth, we investigated the effects of CFTR_inh-172 on the formation and growth of cysts using MDCK cysts as a model system.We tested the effects of CFTR_inh-172 on (i) cAMP-stimulated apical Cl^–currents (ICl_apical),(ii) cell proliferation and (iii) cyst growth, as described previously (Li & Sheppard 2002), with two exceptions. First, we used media containing forskolin (10 µM) and either 0.01 or 10% FBS for cell proliferation assays. Second, in some studies of cyst growth, CFTR_inh-172 was present from day 0 instead of being added at day 6. In all studies, we used CFTR_inh-172 (10 µM), a concentration that inhibits maximally CFTR-mediated Cl^–secretion (Ma et al. 2002). As a control, we studied glibenclamide (100 µM), a nonspecific inhibitor of CFTR.First, in the presence of a Clconcentration gradient, forskolin (10 µM) generated robust ICl_apical in nystatin-permeabilised MDCK epithelia. Both CFTR_inh-172 and glibenclamide inhibited ICl_apical by similar amounts (CFTR_inh-172, 44±1%; glibenclamide, 38±5%; mean±SEM; n = 5; P > 0.05; Student′s unpaired t-test). Second, both CFTR_inh-172 and glibenclamide inhibited cell proliferation in the presence of 0.01% FBS by >90% (n = 4). However, 10% FBS weakened markedly CFTR_inh-172 inhibition (18±7%, n = 4), but not glibenclamide inhibition (69±8%, n = 4). Third, forskolin (10 µM) stimulated cyst formation and enlargement in collagen gels. Over a six-day period, in the continuous presence of forskolin, CFTR_inh-172 and glibenclamide inhibited cyst growth. However, inhibition by glibenclamide was stronger than that of CFTR_inh-172 (glibenclamide, 90±1%, n = 26; CFTR_inh-172, 67±3%, n = 141; P < 0.05). When cysts were grown in the continuous presence of CFTR_inh-172 from day 0, at day 6, both the volume and number of cysts were reduced (forskolin: volume, 0.002±0.0003 mm³,n = 186, number, 44±4, n = 23; CFTR_inh-172: volume, 0.0004±0.00007 mm³,n = 23, number, 22±2, n = 4; P < 0.05 for forskolin vs. CFTR_inh-172 data). We interpret our data to suggest that CFTR_inh172 inhibits cyst growth, albeit not as potently as glibenclamide, by preventing CFTR-induced fluid accumulation within the cyst lumen. The data also suggest that the drug might inhibit cyst growth partly by slowing cell proliferation.