In rodents, grooming is a complex and ethologically rich behavior, sensitive to stress and various genetic and pharmacological manipulations, all of which may alter its gross activity and patterning. Observational analysis of grooming activity and its microstructure may serve as a useful measure of stress and anxiety in both wild and laboratory animals. Few studies have looked at grooming behavior more than cursorily, though in-depth analysis of the behavior would immensely benefit fields utilizing rodent research. Here, we present a qualitative approach to grooming activity and patterning analysis in mice, which provides insight into the effects of stress, anxiety, and depression on this behavioral domain. The method involves quantification of the transitions between different stages of grooming, the percentages of incorrect or incomplete grooming bouts, as well as the regional distribution of grooming activity. Using grooming patterning as a behavioral endpoint, this approach permits assessment of stress levels of individual animals, allows identification of grooming phenotypes in various mouse strains, and has vast implications in biological psychiatry, including psychopharmacology, genetics, neurophysiology, and experimental modeling of affective disorders.