The vasoconstrictor effects of phenylephrine and histamine were investigated in isolated strips of pulmonary arteries in pigs during ageing. Interactions between phenylephrine-induced responses and arachidonic acid derivatives were also studied by incubating the blood-vessels with indomethacin. Potency (pD2 values) and maximal effects (EmaxX) recorded in 5-week-old piglets (group I, n = 5) with phenylephrine [5.71 +/- 0.17 and 0.76 +/- 0.22 g/mg of dry tissue respectively (mean +/- SEM)] were similar to values found in 12-week-old animals (group 2, n = 5) (5.49 +/- 0.30 and 1.06 +/- 0.27 g/mg of dry tissue respectively). The sensitivity and responsiveness of tissues to this agonist were significantly reduced in 26-week-old mature pigs (group 3, n = 6) as indicated by the decrease in pD2 (3.91 +/- 0.23; P < 0.01) and Emax (0.27 +/- 0.13 g/mg of dry tissue; P < 0.05) values observed in this group. Histamine (10(-3) M)-induced maximal responses (Emax) were significantly higher in group 2 (2.23 +/- 0.49 g/mg) than in group 1 (0.85 +/- 0.11 g/mg; P < 0.05) and in group 3 (0.48 +/- 0.10 g/mg; P < 0.01). In 5-week-old animals, indomethacin (3 x 10(-5) M) significantly (P < 0.05) shifted the concentration-response curve to phenylephrine to the right (0.28 log. units) and depressed contractions to this drug as shown by the significant decrease of 39.5% (P < 0.05) in Emax. This cyclo-oxygenase inhibitor had no effect in other groups.(ABSTRACT TRUNCATED AT 250 WORDS)