In order to ascertain the blood levels and the biologic responses obtained after administration of two noninjectable forms of salmon calcitonin (SCT) (i.e., a nasal spray and a suppository), two doses of 200 IU each were administered at 3 hour intervals nasally to 8 normal subjects, and rectally to 9 normal subjects. Five untreated subjects served as controls. All were given a standardized diet for 2 days before the test. Plasma salmon-calcitonin, ionized calcium, phosphate, sodium, proteins, creatinine, and alkaline phosphatase were measured repeatedly after the administration of the drug. Modifications in fractionated urinary calcium, phosphate, sodium, and creatinine excretions (and hydroxyproline for the 8 subjects treated by the nasal spray) were compared with the values measured on the previous day. Plasma concentrations of SCT were found to increase sharply with both routes of administration, the peaks being high and short after rectal administration, low but more sustained after nasal application. Despite these differences, almost similar biologic effects could be demonstrated: transient hypocalcemia, increased calciuria, phosphaturia, and natriuria. Urinary hydroxyproline excretion decreased. Plasma sodium did not increase, whereas it did in the controls. In conclusion, nasal sprays and suppositories of SCT appear to exert the known biologic effects of SCT, and might be favored for long-term treatment in diseases representing indications for calcitonin therapy.