Co-use of alcohol and cannabis is highly prevalent and often problematic. However, mechanisms underlying their co-use remain unclear. This randomized and crossover study tests cross-substance subjective craving for alcohol and cannabis. A community sample of nontreatment-seeking alcohol and cannabis co-users (N = 30 completers, 40% female) reporting high-risk levels of alcohol and cannabis use completed two experimental sessions in their homes and were monitored remotely using internet meeting technology (i.e., Zoom). The two counterbalanced and randomized sessions were as follows: (a) consumption of a standard alcoholic beverage followed by cannabis cue exposure and (b) consumption (i.e., smoking) of a miniature cannabis cigarette (containing 18%-22% tetrahydrocannabinol), followed by alcohol cue exposure. Participants rated their subjective craving for both alcohol and cannabis at baseline, following alcohol/cannabis administration, and following the presentation of cross-substance-related cues. Repeated measures analysis of variances revealed a statistically significant difference in cannabis craving across time, such that craving for cannabis was significantly higher following cannabis cue reactivity, compared to baseline and following alcohol administration (p's < .001). Similarly, there was a statistically significant difference in alcohol craving across time, such that craving for alcohol was significantly higher following alcohol cue reactivity, compared to baseline and following cannabis administration (p's < .001). Overall, results suggest that individuals who co-use alcohol and cannabis are most sensitive to the cue-induced, rather than the pharmacologically induced effects, of substance administration on cross-substance craving. This pattern of findings does not support a complementarity model. Conversely, these results may be interpreted as indicative of a substitution model for alcohol and cannabis co-use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).