1 The effects of adenosine and adenine nucleotides were studied in rat duodenum from postnatal day 1 to day 70. The mechanical activity of duodenal segments was recorded through an isotonic transducer connected to a polygraphic recorder.2 In rat duodenal segments, adenosine-5'-triphosphate (ATP, 10-M) and adenosine-5'-diphosphate (ADP, 10-M) produced a contractile response on postnatal day 1. This response increased with age, peaking on day 7, followed by a gradual decrease and was non-existent by day 21. In contrast, a relaxant response to ATP and ADP was apparent on day 21, and continued to increase up to day 70. 3 The contraction caused by ATP was inhibited by indomethacin or the P2,-purinoceptor antagonist, reactive blue-2 but not by tetrodotoxin or hyoscine. Thus, it may be mediated by production of prostaglandin through the P2,-purinoceptor. The relaxation produced by ATP was inhibited by reactive blue-2 but not by tetrodotoxin, guanethidine or the P,-purinoceptor antagonist, 8-phenyltheophylline indicating that ATP acts on smooth muscle directly through the P2,-purinoceptor. The pD, for the contractile response to ATP was 5.15 on day 7 and that for the relaxant response, 6.64 on day 70. 4 Adenosine (10-aM) and adenosine-5'-monophosphate (AMP, 1O-4M) elicited no response before day 14. On day 14, both adenosine and AMP produced a small relaxant response which increased with age. The relaxation produced by adenosine was inhibited by 8-phenyltheophylline but not by tetrodotoxin or guanethidine, indicating that it is mediated by an action on the Pl-purinoceptor of smooth muscle. 5 It is evident from these results that in neonatal rat, a contractile response to ATP and ADP occurs initially in the duodenum, followed by a relaxant response to adenosine and AMP on day 14 and to ADP and ATP on day 21. 6 The smooth muscle of rat duodenum may tentatively be concluded to contain separate purinoceptors for adenosine and AMP (Pj) and ADP and ATP (P2) and the responses to P1-and P2-agonists change during the course of development.