A study was conducted to explore some of the load and temperature interaction effects on the fatigue crack growth rate (FCGR) of polycrystalline superalloy IN100. Load interaction testing in the form of single overloads was performed at 316° C and 649° C. Temperature interaction testing was performed by cycling between 316° C and 649° C in blocks of 1, 10, and 100 cycles. After compiling a database of constant temperature, constant amplitude FCGR for IN100, fatigue crack growth predictions assuming no load or temperature interactions were made. Experimental fatigue crack propagation data were then compared with these predictions to assess interaction effects. The fracture mechanisms observed during interaction testing using a scanning electron microscope were compared with the mechanisms present during constant temperature, constant amplitude testing. Overload interaction testing led to full crack retardation at 2.0 × overloads for both 316° C and 649° C testing. Overloading by 1.6 × at both temperatures led to retarded crack growth, whereas 1.3 × overloads at 649° C created accelerated crack growth and at 316° C the crack growth was retarded. One block alternating temperature interaction testing grew significantly faster than the non-interaction prediction, while 10 block alternating temperature interaction testing also grew faster but not to the same extent. One hundred block alternating testing grew slower than non-interaction predictions. Possible explanations for the interaction effects responsible for the observed crack growth acceleration and retardation are discussed.