FK506 potently inhibits calcineurin activity in HdhQ111/Q111 neurons. Cortical primary cultures of neurons from knock-in Huntington's disease mice were plated with B27 media for 72 h and next treated with various concentrations of FK506, 1 μM, 0.3 μM or 0.1 μM. After 1 h of incubation cells were lysed and processed to determine calcineurin activity. Results show a significant reduction in calcineurin activity in HD neurons for all tested concentration with no significant differences between concentrations. Results were expressed as percentage of calcineurin activity per gram of tissue. (**p < 0.01 for 1 μM, *p < 0.05 for 0.3 μM and 0.1 μM FK506 concentrations).