Hemoglobin and cytochrome P-450 have in common heme structure (i.e. protoporphyrin (IX), binding ability to molecular oxygen or carbon monoxide and enzyme-like activity (i.e. aniline hydroxylation; J.B.C. 251 3442, 1976). We have already reported the interactions between hemoglobin and several drugs, aminopyrine, aniline and steroid hormones, as determined from the spectral changes of hemoglobin. Similar results were obtained with many other drugs. Difference spectra of methemoglobin induced by most chemicals tested had a trough at 402 approximately 403 nm and a peak at 420 approximately 430 nm. Methanol and ethanol formed a peak at 403 nm and a trough at 420 nm. Difference spectra of oxyhemoglobin induced by most chemicals tested had a peak at 400 approximately 403 nm and a trough at 420 nm. Each of steroid hormones and amino acids tested induced a characteristic spectral change of methemoglobin or oxyhemoglobin. The effect of drug-administration on oxygen affinity of hemoglobin was then examined. We measured oxygen half saturation pressure (P50) using whole blood or purified hemoglobin. Addition of meclofenoxate HCl, PAS-Na and IHMS to purified hemoglobin solution increased P50. Whole blood samples, before and one hour after drug-administration, from 33 inpatients, 13 outpatients and 20 normal subjects (not on drug-administration) were used to determine delta P50 of 12 outpatients were within normal range (-0.5 approximately +0.5 mmHg). Those of 14 inpatients, however, were distributed out of range. The determination of delta P50 may be useful as a screening test for inappropriate drug-administration.