A thermal-mechanical fatigue (TMF) testing system has been developed which is capable of studying the fatigue behaviors of gas turbine materials under simultaneous changes of temperatures and strains (or stresses). Furthermore, an advanced alternating current potential difference (ACPD) measurement technique has been developed successfully to perform on-line monitoring of fatigue crack initiation and growth in specimens tested under isothermal and TMF conditions. In this paper, the basic principles of the ACPD technique as well as all the relevant experimental procedures for performing ACPD measurements, including probe setup, choice of alternating currents (AC) and frequencies, noise rejection, data acquisition, and signal processing, are described. The linear relationship between ACPD signals and crack lengths, as well as the effects of thermal cycling on the ACPD signal, are presented and discussed. The capabilities of the TMF and ACPD systems are well illustrated by fatigue crack initiation and growth test results under isothermal and TMF conditions. These tests were performed on two titanium forgings, Ti-6Al-4V (Ti64) and Ti-6Al-2Sn-6Mo (Ti6246), respectively. Alloy Ti64 was TMF cycled between 150 and 400°C, while Ti6246 was cycled between 200 and 482°C. The resolution for detecting crack initiation at the root of notches was found to be 50 μm with 95% confidence while the resolution for crack growth was 2 μm per mV change of ACPD. An environmental assisted cracking model applied to TMF crack growth is proposed for rationalizing the data.