1. The effects of Cd2+ on Ca2+ uptake was compared with that of D-600 and KCN in guinea-pig taenia coli. Cd2+ inhibited both the phasic and tonic K+ responses, however, D-600 and KCN preferentially inhibited the tonic response. 2. Cd2+ (2 x 10(-6) M) which had no effect on the tissue ATP concentration, inhibited La3+ resistant residual Ca2+ binding at the high and low affinity site. Cd2+ (10(-5) M) which decreased the tissues ATP concentration, markedly inhibited Ca2+ binding at the low affinity site. 3. Both D-600 and KCN showed a greater inhibitory effect on Ca2+ binding at the low affinity site than at the high affinity site. 4. These findings suggest that Cd2+ at low concentration may inhibit Ca2+ influx through Ca2+ channel at surface membrane while at high concentrations (greater than 10(-5) M), Cd2+ would inhibit the accumulation of Ca2+ into low affinity sites relating to energy metabolism at mitochondria.