Polydrug use is an important public health issue since it has been linked to significant adverse health outcomes. Recently, club drugs, including ketamine and other drugs used in dance/rave scenes, have been identified as key substances in new types of polydrug using patterns. While seemingly a self-explanatory concept, "polydrug" use constitutes multiple drug using practices that may impact upon health risks. Ketamine, a club drug commonly administered intranasally among youth for its disassociative properties, has emerged as a drug increasingly prevalent among a new hidden population of injection drug users (IDUs). Using an ethno-epidemiological methodology, we interviewed 40 young (<25 years old) ketamine injectors in New York during 2000-2002 to describe the potential health risks associated with ketamine and polydrug use. Findings indicate that ketamine was typically injected or sniffed in the context of a polydrug using event. Marijuana, alcohol, PCP, and speed were among the most commonly used drugs during recent ketamine using events. Polydrug using events were often quite variable regarding the sequencing of drug use, the drug combinations consumed, the forms of the drug utilized, and the modes of administrating the drug combinations. Future research should be directed towards developing a more comprehensive description of the risks associated with combining ketamine with other drugs, such as drug overdoses, the transmission of bloodborne pathogens, such as HIV and HCV, the short- and long-term effects of drug combinations on cognitive functioning, and other unanticipated consequences associated with polydrug use.