The passage of 125I-labelled arginine-vasopressin (AVP) and its analogues desmopressin (DDAVP) and desglycinamide arginine-vasopressin (DGAVP) into cerebrospinal fluid (CSF) has been studied in the dog. After intravenous injection or infusion of these peptides radioactive sustances were found in the CSF in amounts ranging from 0·5 to 1·4% of the total plasma radioactivity. However, only DDAVP could be identified in the CSF as the unmetabolized peptide. This observation may be related to the long plasma half-life of DDAVP which was found to be 50 min, compared with a half-life of 13 min for AVP and 8 min for DGAVP. After the intranasal administration of either [3H]AVP or 125I-labelled AVP similar results were obtained. Radioactivity was again present in the CSF but no AVP could be identified. These observations showed that the intranasal route of administration provides no increased access to the CSF. The existence of a blood–CSF barrier to AVP is confirmed and indicates that the concentrations of the hormone normally found in CSF arise from sources other than the blood.