According to our present knowledge hypometabolism and hypothermia in uremia are most probably due to direct actions of toxic substances at the cellular level. A cardiovascular etiology seems less possible. A similar reduction of oxygen consumption as observed in uremia can be produced by 5 mg/kg body wt. indole i.p. Acetoine, m- and p-cresol, methylguanidine and putrescine do not reduce oxygen consumption even at tenfold higher doses. Some combinations of these substances, however, are effective when given only 10 mg/kg body wt. each. The effects in vivo cannot be reproduced by employing in vitro systems.