The fundamentals of acoustic emission (AE) analysis of fatigue cracking were applied to Ti-6Al-4V. The effect of microstructure on the characteristics of the AE events generated and the failure mechanisms which produced AE in Ti-6Al-4V were established. Lamellar microstructures generated one to two orders of magnitude more emission than equiaxed microstructures. The combination of larger grain size, more continuous alpha/beta interfaces, more tortuous crack-front geometry, cleavage and intergranular fracture in lamellar microstructures accounts for the greater amount of emission. For lamellar microstructures, most AE events were generated in the upper 20% of the stress range, whereas in equiaxed microstructures, most events were generated at lower stresses. Most AE events were generated during crack opening and also at low stresses. AE events having high level intensities were also generated at stresses other than the peak stress. This is because in titanium alloys, which have both high strength and toughness, AE events are generated from both plastic zone extension and crack extension.