This paper focuses on examining the influence of gender and the type of familiarity of individuals on their perception of mental disability, particularly that of trisomy 21. A sample of 100 subjects was used for the study, some of whom are undergoing training at the Institute. National Social Training Institute (NSTI) and others are individuals belonging to the immediate environment of children with trisomy 21. These groups of subjects were obtained using the reasoned choice sampling technique which comprises of 50 men and 50 women between 21 and 54 years old. An identification questionnaire was used to determine the sex and type of familiarity of the subjects. The perception of Trisomy 21 is, in turn, assessed by a questionnaire developed with reference to that of Hetebrij and Racine (2011). The results obtained indicate that the influence of type of familiarity on the perception of trisomy 21 is significant, while that of sex is not. Such results suggest considering these factors in the care of people with disabilities in general and those with trisomy 21 in particular.