were surgically removed under anaesthesia at various times within 24 hours of treatment and thin tumor slices were prepared and immediately examined without fixation under an optical microscope at the termination of experiments 16 21 days the mice were sacrificed and the tumors livers and spleens were excised and weighed body weight was monitored throughout the treatment period the student t test was utilized assuming a 95 confidence level p lt 0 05 as the requirement for significant comparative differences mice bearing palpable tumors at 8 14 days after transplant were examined without further treatment or at 4 10 hours after administration of 1 u00d7 10 4 u 0 1 ml mouse of hr tnf neither untreated nor tnf treated mice showed gross morbidity changes outside the tumor area but examination of thin slices of the tumors from hr tnf treated mice showed pronounced changes in the tumor vasculature beginning at about 4 hours post hr tnf treatment these changes consisted of localized areas of vasculature showing constriction or enlargement and occasional exuding of blood elements within the vasculature these observations suggested that the tumor localized hemorrhagic effect of hr tnf occurs early as compared to the 20 24 hours that appears necessary for cell killing by hr tnf in vitro the vasculature effects produced by hr tnf treatment in vivo appeared to be rendered more pronounced by treatment of the animals with eaca the antitumor activity of intravenous tnf in conjunction with orally administered eaca was tested palpable meth a sarcoma bearing mice were treated with 3 u00d7 10 3 units tnf or 1 u00d7 10 4 units tnf and compared with these same doses combined.