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More than 85% of Ethiopia's population lives in rural areas and literacy levels in the country are relatively low. Despite this, little is known about levels of knowledge in regard to HIV/AIDS and condom use among illiterate and low-literate rural individuals. We conducted a cross-sectional study among 200 illiterate to semi-literate women, ages 13 to 24, from two rural communities in the Amhara region of northwestern Ethiopia. Nearly all the women had heard about HIV and AIDS. Among the illiterate individuals (n = 54), 24% did not know that HIV was the cause of AIDS and 48% did not know that HIV could be transmitted by sexual intercourse without a condom with an HIV-infected person. Among the same group, 59% did not know what a condom is. Literacy had a strong positive association with knowledge of HIV transmission and condoms. Thus, due to a generally higher level of literacy (grade 5–8 attainment), very young women (ages 13–20) had better knowledge of HIV transmission and condoms than did women ages 21–24 who by comparison were less literate. Given poor knowledge of HIV transmission and condoms among illiterate and low-literate women in Amhara, targeted HIV-prevention interventions are needed in this region.