Bacteria exposed to the spaceflight environment have been shown to have an increased growth rate and an increased resistance to antibiotics. The mechanism of resistance has not yet been identified, as the resistance is quickly lost upon return to Earth. To more fully characterize the spaceflight-induced resistance to antibiotics, 4 species of bacteria were exposed to microgravity for 4 months on the Space Station MIR. Upon return to Earth, these cultures were challenged with a suite of 12 antibiotics of varying modes of action. In contrast to reports from short-term space flights, we find that long-term exposure to microgravity causes bacteria to become more susceptible to most, but not all, antibiotics. Each species responds differently to the suite of antibiotics, frequently becoming less resistant, but occasionally more resistant to the antibiotic. A pattern enabling prediction of response is not yet discernible. While contradicting the results from short-term pure culture research, this experiment confirms results from astronaut and cosmonaut skin flora samples.