Ten germ-free pigs and 10 conventionally reared pigs were fed one of two nutritionally balanced diets containing either 16 ppm Cu (basal) or 283 ppm Cu (high-Cu) to evaluate the physiological relationships between Cu and microbiological environment. Germ-free pigs tended to have higher ADG and average daily feed intake (ADFI) than conventionally reared pigs. Feeding the high-Cu diet tended to reduce ADG and ADFI in germ-free pigs but it increased ADG and ADFI in conventionally reared pigs. Hemoglobin and hematocrit were higher in germ-free pigs than in conventionally reared pigs (P less than .001), and hematocrit (P less than .01) and erythrocyte count (P less than .06) were reduced by feeding the high-Cu diet. Germ-free pigs had lower total leukocyte count (P less than .01) and the relative percentages of differentiated leukocytes were altered compared with conventionally reared pigs. Feeding the high-Cu diet increased the percentage of band neutrophils and monocytes in germ-free pigs but reduced the percentage of these cells in conventionally reared pigs (P less than .04). Germ-free pigs had higher concentrations of Cu and Zn in liver and plasma (P less than .001) and greater plasma ceruloplasmin oxidase activity (P less than .001) than conventionally reared pigs did. The high-Cu diet increased liver Cu and Zn (P less than .001) and plasma Cu (P less than .001) and reduced liver and plasma Fe (P less than .05). Organ weights (g/kg BW) differed between germ-free and conventionally reared pigs, and feeding the high-Cu diet reduced thymus weights (P less than .002). Intestinal weight and thickness were reduced in germ-free pigs, and feeding the high-Cu diet generally reduced villus height and width and crypt depth in germ-free pigs, whereas it increased these measurements in conventionally reared pigs.