The fungal toxin ophiobolin A reacts with the epsilon-amino group of lysine to give a conjugated enamine produce with lambda max at 272 nm and a molar extinction of 19,200 per M/cm. 2. Bovine brain calmodulin reacts with ophiobolin A to give a lambda max at 272 nm. 3. One mol of calmodulin reacts with two moles of ophiobolin A. Reaction of 1 mol of ophiobolin A inactivates 1 mol of calmodulin. 4. Ophiobolin A-treated calmodulin is resistant to tryptic cleavage at lysine 77. 5. Ophiobolin A also inhibits Dictyostelium calmodulin which has glutamine instead of lysine at residue 77.