Acute and chronic infusions of a lipophilic analogue of cyclic AP (dibutyryl cyclic AMP) into cannulated afferent lymphatics of popliteal lymph nodes of sheep have reduced the output of both small and blast lymphocytes into efferent lymph and have tended to reduce the volume of efferent lymph flow (collected by chronic cannulation). Similar infusions of a cyclic GMP analogue (8-bromo cyclic GMP) have increased the output of both small and blast lymphocytes into efferent lymph and the volume of efferent lymph flow. It is suggested that cyclic nucleotide metabolism of lymphocytes and of vascular endothelium may play an important role in the regulation of lymphocyte traffic through peripheral lymph nodes in vivo and that secondary alterations in cellular cyclic nucleotide levels may be a common pathway by which the many and varied agents arriving in afferent lymph may affect lymphocyte traffic.