1. The aim of this study was to investigate the smooth muscle relaxant effects of the novel, selective phosphodiesterase (PDE) type 4 inhibitor, RP 73401 in comparison with the classical PDE 4 inhibitor, rolipram, the non-selective PDE inhibitor, theophylline and the beta-adrenoceptor agonist, isoprenaline on the human, isolated bronchus. 2. At resting tone, the rank order of potency (pD2) for the relaxants was RP 73401 > or = rolipram > or = isoprenaline >> theophylline. In terms of maximum relaxation produced (Emax) the PDE 4-selective inhibitors were similar, but the maximal effects (70-75% of theophylline, 3 mM) were lower than that observed with isoprenaline (98% of theophylline, 3 mM) or theophylline itself (100%). 3. On the human isolated bronchus pre-contracted with acetylcholine (ACh, 0.1 or 1.0 mM), the rank order of potency remained the same. The maximal responses to RP 73401 and rolipram were however markedly reduced (Emax 39.9-46.6%) compared with isoprenaline (Emax 79-85%). 4. In tissues pre-contracted with ACh (0.1 mM), RP 73401 and rolipram (10(-9)-10(-7) M) significantly and concentration-dependently increased tissue sensitivity to isoprenaline. RP 73401 and rolipram were similar in potency. Both selective PDE 4 inhibitors also significantly increased the maximal relaxant effects of isoprenaline. These effects were not observed with the PDE 3 inhibitor, siguazodan. 5. In terms of retention by tissues (an index of duration of action), the onset of action of RP 73401 (2.11 +/- 0.53 min) and rolipram (1.70 +/- 0.45 min) was significantly slower than that of isoprenaline (0.33 +/- 0.06 min) or theophylline (1.17 +/- 0.25 min). The retention of RP 73401 (89.0 +/- 21.9 min) on the human isolated bronchial tissues after washing was however dramatically longer than that of rolipram (18.3 +/- 4.5 min), theophylline (3.43 +/- 0.58 min) or isoprenaline (2.81 +/- 0.31 min). 6. These data indicate that RP 73401 is a potent and long acting relaxant of human bronchial muscle in vitro. RP 73401 is more potent than the classical PDE 4-selective inhibitor rolipram and the non-selective PDE inhibitor theophylline and is retained in bronchial tissue for a much longer period of time.