Two main trials and three preliminary experiments were conducted in order to examine adverse effects of excess lysine in 140- to 150-kg Holstein bull calves. The animals had been trained to maintain reflex closure of the reticular groove after weaning and were fed a corn and soybean meal diet. In Trial 1 (n = 30), administration via the reticular groove of 0 to 64 g/d of lysine as L-lysine monohydrochloride resulted in a linear decrease in DMI and N utilization efficiency, with notably lower values at 64 g/d, although ADG and gain/feed ratio were not affected. Plasma arginine and ornithine did not decrease but rather increased over that range. Free lysine but not free arginine was detected in urine. In addition, free ornithine was excreted into urine only when 64 g/d was administered. Unexpectedly, severe but transient diarrhea occurred when 64 g/d of lysine were administered. Preliminary experiments revealed that a single administration of more than 32 g of lysine as L-lysine monohydrochloride could result in diarrhea, and the diarrhea was proven to be due to the lysine itself and not to the HCl portion. In Trial 2 (n = 15), a single administration of 40 or 60 g of lysine as L-lysine monohydrochloride resulted in increased fecal excretion of free lysine and ornithine, especially the latter, although free arginine was not detected in feces. These results suggested that diarrhea could occur almost concurrently with an imbalance in calves when 64 g/d of lysine was administered. However, lysine did not antagonize arginine at that level or at lower levels. The remarkable increase in fecal ornithine may be somehow related to the development of diarrhea from excess lysine.