A series of eleven undeca- and four hexapeptide antagonists of substance P (SP) have been assayed by the SP-induced behavioural test in mice. When 2 nmol of [D-Arg1, D-Pro, D-Trp, Leu]-SP (SP 1-11 I) was intrathecally injected together with SP (0.1 nmol), SP-induced response which consists of scratching, biting and licking was markedly inhibited. [D-Trp, Leu]-SP 6-11 (SP 6-11 I) given in a dose of 2 nmol was also inhibited the SP-induced response to the same degree as SP 1-11 I. Some of SP 1-11 or SP 6-11 analogues substituted with fluorine in positions 7 and/or 8 maintained the antagonistic effect of SP 1-11 I or SP 6-11 I, though the others were weaker. Intrathecal administration of SP 1-11 I and SP 6-11 I resulted in long-lasting antinociceptive effects as measured by the tail-flick test. Fluorine-containing SP analogues were less potent than the above two analogues in producing antinociception. These results suggest that the antagonistic effect of SP analogues on the SP-induced nociceptive response do not necessarily relate to antinociceptive activity at the spinal cord level.